TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8913	26962;26963;26964	chr2:178713921;178713920;178713919	chr2:179578648;179578647;179578646
N2AB	8596	26011;26012;26013	chr2:178713921;178713920;178713919	chr2:179578648;179578647;179578646
N2A	7669	23230;23231;23232	chr2:178713921;178713920;178713919	chr2:179578648;179578647;179578646
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-74
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.0902
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
C/G	rs775565721	-2.599	0.92	D	0.726	0.34	0.819116995716	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.63655E-04	None	0	0	0
C/G	rs775565721	-2.599	0.92	D	0.726	0.34	0.819116995716	gnomAD-4.0.0	6.84347E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	9.27967E-05	3.31356E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
C/A	0.4225	ambiguous	0.4568	ambiguous	-1.916	Destabilizing	0.579	D	0.505	neutral	None	None	None	None	N
C/D	0.7608	likely_pathogenic	0.8149	pathogenic	-0.451	Destabilizing	0.939	D	0.783	deleterious	None	None	None	None	N
C/E	0.8994	likely_pathogenic	0.92	pathogenic	-0.33	Destabilizing	0.939	D	0.786	deleterious	None	None	None	None	N
C/F	0.3312	likely_benign	0.3562	ambiguous	-1.2	Destabilizing	0.996	D	0.771	deleterious	N	0.497480389	None	None	N
C/G	0.2245	likely_benign	0.262	benign	-2.244	Highly Destabilizing	0.92	D	0.726	prob.delet.	D	0.529325806	None	None	N
C/H	0.7247	likely_pathogenic	0.7649	pathogenic	-2.156	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
C/I	0.5707	likely_pathogenic	0.6344	pathogenic	-1.063	Destabilizing	0.969	D	0.768	deleterious	None	None	None	None	N
C/K	0.8961	likely_pathogenic	0.919	pathogenic	-1.089	Destabilizing	0.939	D	0.781	deleterious	None	None	None	None	N
C/L	0.5852	likely_pathogenic	0.6183	pathogenic	-1.063	Destabilizing	0.969	D	0.691	prob.neutral	None	None	None	None	N
C/M	0.7381	likely_pathogenic	0.7624	pathogenic	-0.007	Destabilizing	0.997	D	0.725	prob.delet.	None	None	None	None	N
C/N	0.6902	likely_pathogenic	0.751	pathogenic	-1.126	Destabilizing	0.939	D	0.789	deleterious	None	None	None	None	N
C/P	0.9929	likely_pathogenic	0.994	pathogenic	-1.322	Destabilizing	0.991	D	0.788	deleterious	None	None	None	None	N
C/Q	0.7767	likely_pathogenic	0.8004	pathogenic	-0.985	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
C/R	0.5888	likely_pathogenic	0.6438	pathogenic	-0.973	Destabilizing	0.988	D	0.786	deleterious	N	0.51021997	None	None	N
C/S	0.2561	likely_benign	0.2973	benign	-1.7	Destabilizing	0.159	N	0.393	neutral	N	0.456134769	None	None	N
C/T	0.4132	ambiguous	0.4665	ambiguous	-1.386	Destabilizing	0.759	D	0.685	prob.neutral	None	None	None	None	N
C/V	0.4607	ambiguous	0.5255	ambiguous	-1.322	Destabilizing	0.969	D	0.709	prob.delet.	None	None	None	None	N
C/W	0.7667	likely_pathogenic	0.8	pathogenic	-1.176	Destabilizing	0.999	D	0.717	prob.delet.	N	0.498240857	None	None	N
C/Y	0.5384	ambiguous	0.5974	pathogenic	-1.191	Destabilizing	0.996	D	0.764	deleterious	N	0.484731732	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.